Interleukin-12 (IL-12) is a pivotal cytokine that mediates IL-12 receptors for producing proinflammatory cytokines, or promotes specific lymphocyte responses. One of its key roles is to promote type 1 T helper cell (Th1) responses and, hence, cell-mediated immunity. Overproduction of IL-12 will cause excessive Th1 responses, which may result in inflammatory disorders, such as autoimmune diseases. Gately et al. 1998, Annu Rev lmmunol. 16, 495. IL-12 is therefore an ideal target for pharmacological intervention in the therapy of inflammatory diseases caused by excessive proliferation of Th1 cells. Trembleau et al. 1995; Immunol. Today 16, 383, and Adorini et al. 1997; Chem. Immunol. 68, 175. Overproduction of IL-12 and the resultant Th1 type immune responses can be suppressed with several pharmacological approaches including modulation of intracellular cyclic AMP levels, and inhibition of glucocorticoids and nuclear factor-kappaB. Hasko et al. 1999, Br. J. Pharmacol 127, 1295. It is desirable to identify a new compound for treatment of IL-12 overproduction-related disorders.
This invention is based on the identification of a new compound from a library of plant extracts, which were screened for their abilities to inhibit IL-12 production.
An aspect of this invention relates to the compound, epoxyvibsanin B, of the formula: 
This compound can be either synthesized from organic chemicals or isolated from a natural source, e.g., Caprifoliaceae vibrunum Awabuki. 
Another aspect of this present invention relates to a method of treating an IL-12 overproduction-related disorder with epoxyvibsanin B. The method includes administering to a subject in need thereof an effective amount of this compound.
Epoxyvibsanin B is formulated into a pharmaceutical composition before it is administered to a subject in need of treatment of an IL-12 overproduction-related disorder, which includes inflammatory (both acute and chronic) such as autoimmune diseases. Thus, also within the scope of the present invention is a pharmaceutical composition that contains an effective amount of epoxyvibsanin B and a pharmaceutically acceptable carrier for use in treatment of IL-12 overproduction-related disorders. The present invention also encompasses the use of epoxyvibsanin B for the manufacture of a medicament for treatment of the above-mentioned disorders.
Other advantages or features of the present invention will be apparent form the following detailed description thereof.